Alcoholism is a chronic disorder characterized by repeated episodes of relapse to alcohol consumption. Potential precipitators of relapse include cues paired with past alcohol use. Subsequent exposure to these stimuli could induce a state of alcohol craving that results in reinstatement of alcohol us. The goals of this proposal are to determine the biological bases of how conditioned cues elicit or inhibit drug-seeking. The long- range objectives of this study are to determine the neurocircuits that regulate the modulation of EtOH-seeking by conditioned cues. The overall hypotheses are that there are two distinct systems that integrate environmental cues that promote or inhibit EtOH-seeking, and that each system is comprised of separate neurocircuits and neurotransmitter systems. These hypotheses will be tested primarily using the alcohol- preferring (P) rat, which demonstrates high alcohol drinking behavior and robust EtOH-seeking and relapse behaviors. Proposed experiments will determine the effects of environmental cues (conditioned excitation and conditioned inhibition) on the expression of context-induced seeking. Proposed experiments will determine the neurochemical consequences of exposure to conditioned cues that promote or inhibit EtOH-seeking. In addition, the proposed experiments will identify the neurotransmitter characteristics of neurons activated by presentation of cues that promote or inhibit EtOH-seeking. Further experiments will determine the effects of altering activity at candidate receptors in discrete brai regions on the ability of conditioned cues to alter EtOH- seeking. Understanding the complex factors that underlie EtOH-seeking behaviors and the ability of environmental cues to potentiate or suppress EtOH-seeking will contribute toward the development of therapeutic strategies to reduce 'craving' and alcohol relapse.